Chemotherapy For Retinoblastoma Research Articles

Amniotic Membrane Augmentation for Enucleation After Chemotherapy in Retinoblastoma.

To describe amniotic membrane augmentation for enucleation after chemotherapy in retinoblastoma. This was a retrospective study of patients with retinoblastoma who underwent enucleation. The study also evaluated the utility of amniotic membrane grafting in enucleation after chemotherapy in eyes with retinoblastoma. In this study, 110 eyes of 107 patients were analyzed, and 49 patients had previous systemic chemotherapy, 13 eyes had previous intra-arterial chemotherapy, and 7 eyes had external beam radiation. Amniotic graft was used in 8 eyes (5 following IAC, 2 following systemic chemotherapy, and 1 after both). After IAC, 3 of 7 eyes without amniotic graft had implant exposure compared to 0 of 6 eyes with amniotic graft (P = .05). Pathological examination of the conjunctiva after intra-arterial chemotherapy showed goblet cell hypoplasia that hinders wound healing. Amniotic membrane augmentation improves wound integrity in patients with retinoblastoma, especially following intra-arterial chemotherapy. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XXX-XXX.].

Assessment of Retinal Microvasculature and Choroidal Vascularity After Intra-arterial Chemotherapy for Retinoblastoma: Retinal and Choroidal Vascular Assessment After IAC for RB

PurposeTo evaluate changes in retinal microvascular density and choroidal vascularity in patients with retinoblastoma (RB) after intra-arterial chemotherapy (IAC). DesignRetrospective clinical cohort study. MethodsThis study included 12 unilateral RB eyes treated with IAC (RB tumour), 12 contralateral normal eyes (RB fellow), and 12 healthy controls. The macular retinal thickness and retinal microvascular structure, including foveal avascular zone (FAZ) area, the macular and peripapillary superficial vessel density (SVD) and deep vessel density (DVD), were measured by optical coherence tomography angiography (OCTA). The choroidal thickness (ChT) and choroidal vascularity, including total choroidal area (TCA), luminal area (LA), stromal area (SA) and Choroidal Vascularity Index (CVI), were measured by spectral-domain optical coherence tomography (SD-OCT). A comparison among the three groups was conducted, while the correlations among the parameters were analyzed. ResultsBetween the three cohorts, the foveal retinal thickness, the SVD, DVD, ChT, TCA, LA, SA and CVI were significantly lower in RB tumour compared to RB fellow and the control eyes (all P<0.01). There were no significant differences in the parameters between the contralateral and control eyes. The correlation analyses indicated a significant negative correlation between the total melphalan dose and foveal and parafoveal DVD, ChT, and LA. ConclusionsThe retinal microvascular density and choroidal vascularity were lower in unilateral RB treated with IAC, and seemed to be related to the total melphalan dose. Moreover there were no measurable changes in the contralateral eyes.

Metastatic Death Following Ophthalmic Artery Chemotherapy for Retinoblastoma: A Systematic Review and Meta-analysis

Objective: The use of ophthalmic artery chemotherapy (OAC) as a front-line and salvage therapy for retinoblastoma has grown. However, the risk of metastatic death in these patients remains unclear. Materials and Methods: This study of metastatic deaths in OAC may benefit physicians managing retinoblastoma patients. A literature search of Medline, Scopus, Science Direct, and CINAHL was conducted from conception until November 2023. The primary outcome was metastatic death in patients treated with OAC. Results: From the 219 evaluated articles, nine met the inclusion criteria. A total of 596 (635 eyes) patients were treated with OAC; and 20 cases resulted in death due to metastasis of the retinoblastoma. The metastatic mortality rate was 2.5% (95% confidence interval: 0.8%-4.2%) which was statistically significant (p &lt; 0.05). The central nervous system was the most common site of metastasis, followed by multiple sites of metastasis. Conclusion: OAC treatment is associated with the risk of metastatic death, but it is lower than the overall mortality rate of retinoblastoma. Further studies to identify the risk of metastasis are needed.

Efficacy evaluation of carboplatin -etoposide Co-loaded PLGA microparticles for subconjunctival chemotherapy in retinoblastoma

Systemic chemotherapy for retinoblastoma comes with various haematological side effects, hence, require newer treatment approaches. This study developed carboplatin (CPT) and etoposide (ETP) loaded biodegradable PLGA microparticles as a combination therapy for extended action decreasing frequency of administration. CPT and ETP loaded PLGA microparticles (CE-MIP) were prepared by emulsification-spray drying technique. The optimized drug loaded PLGA microparticles were characterized for particle size (3–14 μm), zeta potential (−23.0 to −34.2 mV), entrapment efficiency (ETP - >80 % & CPT - >60 %) and in vitro release (CPT – 4 h & ETP – 72 h). In vitro cytotoxicity studies of CE-MIP showed greater anti-cancer effect (25.33 % cell viability) compared to plain drug mixture (38.56 % cell viability) in Y-79 cells. In WERI-Rb cell lines, the CE-MIP and plain drug mixture at 100 μM showed percent cell viability as 37.82 % and 66.08 % respectively. In the soft agar assay, the CE-MIP treatment demonstrated a significant reduction in the number of colonies (∼50 % reduction) formed compared to control. In orthotropic mouse model of retinoblastoma, the apoptotic effect of subconjunctival CE-MIP (15.7 %) was greater compared to control (7.9 %). Mean tumor burden of CE-MIP treated eyes was significantly smaller compared to the untreated control eyes showing the anti-tumor efficacy of developed CE-MIP.

Enhanced anti-tumor activity of transferrin/folate dual-targeting magnetic nanoparticles using chemo-thermo therapy on retinoblastoma cancer cells Y79

Malignant neoplasms are one of the main causes of death, especially in children, on a global scale, despite strenuous efforts made at advancing both diagnostic and therapeutic modalities. In this regard, a new nanocarrier Vincristine (VCR)-loaded Pluronic f127 polymer-coated magnetic nanoparticles conjugated with folic acid and transferrin (PMNP-VCR-FA-TF) were synthesized and characterized by various methods. The cytotoxicity of these nanoparticles was evaluated in vitro and ex vivo conditions. The in vitro anti-tumor effect of the nanoparticles was evaluated by colony formation assay (CFA) and reactive oxygen species (ROS) in Y79 cell line. The results showed that nanoparticles with two ligands conferred greater toxicity toward Y79 cancer cells than ARPE19 normal cells. Under an alternating magnetic field (AMF), these nanoparticles demonstrated a high specific absorption rate. The CFA and ROS results indicated that the AMF in combination with PMNP-VCR-FA-TF conferred the highest cytotoxicity toward Y79 cells compared with other groups (P < 0.05). PMNP-VCR-FA-TF could play an important role in converting externally applied radiofrequency energy into heat in cancer cells. The present study confirmed that dual targeting chemo-hyperthermia using PMNP-VCR-FA-TF was significantly more effective than hyperthermia or chemotherapy alone, providing a promising platform for precision drug delivery as an essential component in the chemotherapy of retinoblastoma.

Lipid-nanoparticles-based co-delivery of black phosphorus quantum dots and melphalan by photothermal therapy combined with chemotherapy for retinoblastoma

Melphalan is an efficient chemotherapeutic agent for retinoblastoma (RB) in clinical practice. However, the problems of drug resistance and poor prognosis caused by long-term treatment of melphalan should not be ignored. At present, it is urgent to find a therapeutic strategy to enhance the curative effect to solve the need for clinical treatment of RB to protect eyesight. Herein, we propose an effective strategy to encapsulate melphalan and black phosphorus quantum dots (BPQDs) with high-biocompatibility liposomes for photothermal therapy (PTT) to enhance cell killing. BPQDs and melphalan were encapsulated using liposomes with a similar structure to the cell membrane, and a lipid nanoparticle with both photothermal and chemical inhibition effects was prepared. The obtained nanoparticle has a spherical shape (particle size range of 82–180 nm) and good stability (encapsulation efficiencies of melphalan of 40 % and BPQDs of 43.7 %). Its temperature increased to 65 °C within 10 min under a 2 W/cm2 laser at 808 nm, exerting photothermal and synergistic effects with melphalan to induce apoptosis of tumor cells. As expected, the prepared nanoparticle effectively inhibits tumor proliferation, upregulates the ki67 expression level, and has an excellent PTT effect on the orthotopic xenograft of WERI-RB-1 cells.

Angiographic characteristics and treatment approach in patients undergoing intra-arterial chemotherapy for retinoblastoma.

To identify the specific clinical and angiographic variables that determine the success of intra-arterial chemotherapy (IAC) in a patient with retinoblastoma. Medical records from patients undergoing intra-arterial chemotherapy for the treatment of retinoblastoma between January 2015 and June 2020 within a large academic ocular oncology practice were retrospectively reviewed. Demographics were recorded together with clinical, ocular, and angiographic variables such as the diameter of the ophthalmic artery (OA), angle of ophthalmic artery takeoff, and branching pattern of ophthalmic vasculature. Forty-four eyes from 33 patients with retinoblastoma treated with IAC were identified. Over the total 32 mean months of follow-up, these patients received 144 total catheterizations and a mean of 3.2 IAC cycles for each eye. The number of IAC cycles and the chemotherapeutic agent used did not vary significantly with worsening International Classification of Retinoblastoma (ICRB) groups (P > 0.1). Cumulative dose did not vary with the ICRB group for eyes treated with melphalan, topotecan, or carboplatin (P > 0.1). A higher ICRB group was associated with a smaller mean ophthalmic artery diameter across all procedures (P = 0.016), and femoral artery diameter did not vary significantly between ICRB groups (P = 0.906). A higher cumulative dose of IAC was significantly associated with a smaller takeoff angle of the OA (melphalan, P = 0.011; topotecan, P = 0.009; carboplatin, P = 0.031) in patients who underwent successful IAC procedures. Ophthalmic artery diameter and femoral artery diameter did not have a significant association (P > 0.1) with higher IAC doses in successful IACs. Cumulative IAC dose was not significantly associated with ophthalmic vasculature branching pattern, presence of choroidal blush, temporary OA vasospasm reported during the procedure, and OA occlusion upon microcatheter placement. In this study, neurosurgical angioanatomy appeared to influence the cumulative dose of chemotherapy needed during IAC for retinoblastoma. In the future, these anatomic variables may be used to guide the frequency of monitoring, dosing, and estimation of recurrence risk.

Intra-arterial chemotherapy for retinoblastoma: Centralization of care is essential.

Intra-arterial chemotherapy for retinoblastoma: Centralization of care is essential.

Incidence and Risk Factors for Neutropenia After Intra-Arterial Chemotherapy for Retinoblastoma

Intra-arterial chemotherapy (IAC) has quickly gained popularity as a mainstay of treatment for retinoblastoma. Intra-arterial chemotherapy has been described as having several advantages over systemic chemotherapy, including reducing systemic toxicity and neutropenia; however, studies on the risk of neutropenia after IAC remain limited. To estimate the incidence of neutropenia after IAC, as well as identify risk factors associated with the development of neutropenia. This case series included pediatric patients with unilateral or bilateral retinoblastoma who were treated with IAC at a single quaternary care center from July 13, 2013, to January 6, 2023. All patients were treated with IAC and underwent multiple IAC cycles depending on treatment response. The primary chemotherapy agent used was melphalan, but topotecan or carboplatin could be used along with melphalan. Melphalan doses were kept to 0.4 mg/kg or less per cycle. After each IAC cycle, complete blood cell counts were obtained within 10 to 12 days and repeated until the absolute neutrophil count (ANC) was greater than or equal to 1000/μL. The primary outcome was the minimum ANC after each IAC cycle. The secondary outcome was the development of severe (grade 3 or 4) neutropenia (ANC <1000/μL). Regression analyses were used to identify associations between variables and outcomes. Receiver operating characteristic curves were used to calculate threshold dose for each chemotherapy agent potentially associated with the development of severe neutropenia. A total of 64 eyes of 49 patients (mean [SD] age, 1.7 [1.2] years; 25 females [51.0%]) with retinoblastoma were treated with 171 cycles of IAC. The mean (SD) nadir ANC was 1325.3 (890.7)/μL and occurred a median (IQR) of 10 (10-14) days (range, 6-28 days) after IAC administration. The frequency distribution of post-IAC neutropenia grades 0, 1, 2, 3, 4, and missing was 31 (18.1% of cycles), 25 (14.6%), 40 (23.4%), 37 (21.6%), 26 (15.2%), and 12 (7.0%), respectively. Factors weakly correlated with a lower ANC were higher melphalan dose (β = -2356 [95% CI, -4120.6 to -611.2]; adjusted R2 = 0.251; P = .01) and higher topotecan dose (β = -4056 [95% CI, -7003.6 to -1344.5]; adjusted R2 = 0.251; P = .006). In this case series of patients with retinoblastoma, the incidence of severe neutropenia after IAC was nearly 40%, which is higher than previously reported. Extended laboratory monitoring may aid in capturing previously overlooked cases of neutropenia. Topotecan may be associated with the development of neutropenia; limiting topotecan doses, especially in the setting of a high melphalan dose, may be beneficial in reducing the risk of neutropenia.

Advancements in super-selective catheterization and drug selection for intra-arterial chemotherapy for retinoblastoma: a 15-year evolution

BackgroundRetinoblastoma (Rb) is the most common primary ocular malignancy of childhood. Left untreated, it is 100% fatal and carries a substantial risk of impaired vision and removal of one or...

Algorithm for evaluating ophthalmic artery pseudo-occlusion during intra-arterial chemotherapy for retinoblastoma.

Intra-arterial chemotherapy infusion for retinoblastoma is typically performed via selective catheterization of the ophthalmic artery. Anastomoses between the external carotid and the ophthalmic arteries have also been utilized when the ophthalmic artery cannot be catheterized directly. However, these are not present in every patient. A 10-month-old boy presented with bilateral retinoblastoma and underwent one round of intra-arterial chemotherapy (IAC) via direct catheterization of the ophthalmic arteries. Combined with adjuvant laser therapy, they experienced symptomatic improvement and tumour regression. However, during subsequent treatment sessions both ophthalmic arteries did not have anterograde flow and attempts to catheterize their origin were unsuccessful. Unfortunately, no targetable anastomoses between the external carotid and ophthalmic arteries were identified for drug delivery. Due to the patient's anatomy, balloon occlusion of the ECA was felt to be unsafe. As a salvage technique, a balloon was inflated in the left internal carotid artery (ICA) distal to the ophthalmic take-off to redirect flow into the ophthalmic. Repeat angiography with the distal ICA occluded showed improved flow into the ipsilateral ophthalmic artery. IAC was then successfully delivered through the left ICA. This case illustrates the importance of utilizing creative endovascular techniques for targeted intra-arterial drug delivery when other conventional measures fail as these patients often have limited, and potentially higher risk, therapeutic alternatives.

Tumor Suppressor Role of INPP4B in Chemoresistant Retinoblastoma.

The chemotherapy of retinoblastoma (RB), a malignant ocular childhood disease, is often limited by the development of resistance against commonly used drugs. We identified inositol polyphosphate 4-phosphatase type II (INPP4B) as a differentially regulated gene in etoposide-resistant RB cell lines, potentially involved in the development of RB resistances. INPP4B is controversially discussed as a tumor suppressor and an oncogenic driver in various cancers, but its role in retinoblastoma in general and chemoresistant RB in particular is yet unknown. In the study presented, we investigated the expression of INPP4B in RB cell lines and patients and analyzed the effect of INPP4B overexpression on etoposide resistant RB cell growth in vitro and in vivo. INPP4B mRNA levels were significantly downregulated in RB cells lines compared to the healthy human retina, with even lower expression levels in etoposide-resistant compared to the sensitive cell lines. Besides, a significant increase in INPP4B expression was observed in chemotherapy-treated RB tumor patient samples compared to untreated tumors. INPP4B overexpression in etoposide-resistant RB cells resulted in a significant reduction in cell viability with reduced growth, proliferation, anchorage-independent growth, and in ovo tumor formation. Caspase-3/7-mediated apoptosis was concomitantly increased, suggesting a tumor suppressive role of INPP4B in chemoresistant RB cells. No changes in AKT signaling were discernible, but p-SGK3 levels increased following INPP4B overexpression, indicating a potential regulation of SGK3 signaling in etoposide-resistant RB cells. RNAseq analysis of INPP4B overexpressing, etoposide-resistant RB cell lines revealed differentially regulated genes involved in cancer progression, mirroring observed in vitro and in vivo effects of INPP4B overexpression and strengthening INPP4B's importance for cell growth control and tumorigenicity.

The Antitumor Effect of Topotecan Loaded Thiolated Chitosan-Dextran Nanoparticles for Intravitreal Chemotherapy: A Xenograft Retinoblastoma Model.

This research intended to fabricate the thiolated chitosan-dextran nanoparticles (NPs) containing topotecan (TPH-CMD-TCS-NPs) to assess the ability of NPs in improving the efficacy of intravitreal chemotherapy of retinoblastoma in a rabbit xenograft model. The coacervation process was used to produce the NPs. The cellular uptake of Cyanine-3 (CY3)-labeled NPs were investigated in human retinoblastoma Y79 cells using confocal microscopy. Also, the prepared TPH-CMD-TCS-NPs were tested in vitro by the tetrazolium dyes II (XTT) and flow cytometry in order to assess their cytotoxicity. In addition, a rabbit xenograft model of retinoblastoma was developed to test the antitumor effectiveness of TPH-CMD-TCS-NPs through intravitreal administration. NPs had a mean diameter, polydispersity index, and zeta potential of 30 4 nm, 0.24 0.03 and +10 3 mV, respectively. NPs (IC50s 40.40 compared to 126.20 nM, P = 0.022) were more effective than free topotecan as a dose-based feature. The tumor reaction to intravitreal chemotherapy with NPs was measured by evaluating the percentage of necrosis in the tumor tissue (91 2%) and vitreous seeds (89 9%) through hematoxylin and eosin (H&E) staining. In comparison with the control group, the TPH-CMD-TCs-NPs treated group showed a significant decrease in tumor volume seven days after the intravitreal injection (P = 0.039). No significant changes were found in the ERG parameters after the intravitreal injection of TPH-CMD-TCs-NPs or TPH (P 0.05). This investigation revealed definitive antitumor efficacy of TPH-CMD-TCS-NPs by intravitreal administration in the rabbit xenograft retinoblastoma model.

Intra-arterial chemotherapy for retinoblastoma: Experience from the pediatric ophthalmology referral center in Malaysia with literature review.

We aimed to analyze our 4-year experience of intra-arterial chemotherapy (IAC) for retinoblastoma (RB) and to examine the tumor response, globe salvage, mortality, and safety profile of IAC in the Malaysian profile. This was a retrospective, interventional case series. A total of 22 eyes of 20 patients with RB who underwent IAC using melphalan and topotecan from January 2018 to December 2021 in Hospital Kuala Lumpur were retrospectively reviewed. Tumor response, globe salvage, mortality, and safety profile of IAC were compared based on the International Classification of Retinoblastoma. The mean patient age at IAC was 21.3 months. An overall globe salvage rate of 63.6% was observed: more specifically, 100% for Group A, 75% for Groups B and C, 66.7% for Group D, and 42.9% for Group E. Poor tumor response after IAC was significantly associated with a lesser chance of globe salvage (P = 0.045). The overall rate of good tumor response following IAC was 77.3%. Specifically, rates of good tumor response in each group were 100%, 75%, 75%, 83.3% and 71.4% in group A, B, C, D and E, respectively. The mortality rate was 5%. Complications (per-catheterization) included cerebral infarct (2.2%), oxygen desaturation (2.2%), vomiting (26.1%), periorbital edema (8.8%), ptosis (6.5%), fever, femoral hematoma, and hyperpigmentation over lid (4.4% each). Four-year experience showed that IAC is a safe and effective method for RB management. Patients with a poor response after IAC may have a lower chance of globe salvage. Careful patient selection is of utmost importance to achieve the best outcome in a setting of limited health-care resources.

Spotlight on Targeted Chemotherapy in Retinoblastoma: Safety, Efficacy, and Patient Outcomes.

As the most common primary intraocular malignancy of childhood, retinoblastoma (RB) has had a complex journey in its management, following a course from enucleation as the first life-saving treatment to numerous globe-salvaging therapies during the last century. Currently, this potentially lethal disease has achieved high survival rates owing to multidisciplinary management and the introduction of neoadjuvant and multimodal chemotherapy. Therefore, the goal of treatment is shifting toward conserving the globe and vision as much as possible. Up until recently, many advanced cases of RB were enucleated primarily; however, targeted chemotherapy via the ophthalmic artery and management of intraocular seeding by local administration of chemotherapeutic agents have revolutionized the globe-conserving therapies. The added benefit of avoiding systemic complications of cytotoxic drugs resulted in these methods gaining popularity, and they are becoming a main part of care in many referral centers. Initially, there were some safety concerns regarding these approaches; however, increasing experience has shown that these modalities are relatively safe procedures and many complications can be averted by changing the choice of the drug and using some prophylactic measures. It is hoped that, in the near future, with advances in early diagnosis and patient-targeted molecular therapies, as well as gene-editing techniques, the patient's vision can be saved even in advanced RB.

Ocular survival after intra-arterial chemotherapy for retinoblastoma improves with accrual of experience and programmatic evolution.

Intra-arterial chemotherapy (IAC) for the treatment of intraocular retinoblastoma has gained recognition as a method to improve ocular salvage; however, there is a paucity of evidence supporting treatment factors prognosticating ocular survival. All patients with retinoblastoma treated with IAC at a single institution between December 2008 and December 2019 were evaluated. Patient demographics, tumor classification, prior treatments, procedural data, other non-IAC therapies, adverse reactions, procedural complications, ocular outcomes, and overall survival were assessed via retrospective chart review. Factors suggestive of increased ocular survival were identified via univariate and multivariate analyses. The impact of accrued treatment experience was evaluated by grouping eyes by the respective year, IAC treatment was initiated. Forty-nine eyes of 43 patients were treated for retinoblastoma with IAC (256 total procedures). At least grade 3 neutropenia was observed following 19% of IAC procedures. The risk of neutropenia was not statistically different between single or multidrug IAC. Comparing those who received balloon-assisted intra-arterial chemotherapy (bIAC) in more than two-thirds of cycles to those who did not, the risk of arterial access site complications was not statistically different. Multivariate analysis revealed a significantly lower risk of enucleation associated with treatment era in years (hazard ratio [HR]=0.52-1.00, p<.05) and laser therapies (HR=0.02-0.60, p<.05). Ocular survival rates in patients treated with IAC for retinoblastoma at our institution have increased over time. Accrued treatment experience and programmatic changes have likely contributed. Larger, prospective series may lead to a better understanding of factors that consistently contribute to better ocular salvage.

Delayed subcutaneous emphysema, mediastinal emphysema and pneumothorax after tracheal intubation in a child: a case report

Subcutaneous emphysema and mediastinal emphysema and/or pneumothorax after mechanical ventilation through endotracheal intubation is not uncommon. However, cases of delayed mediastinal emphysema and subcutaneous emphysema after extubation and their further development into pneumothorax have rarely been reported, especially in children. Given this, we provide such a case for the reference of clinicians. We report a case of a 2-year-old girl with no abnormalities at the preoperative examination, who developed subcutaneous emphysema and mediastinal emphysema 4 hours after recovery from general anesthesia due to ophthalmic arterial infusion chemotherapy for retinoblastoma, and bilateral pneumothorax 12 hours later. The patient recovered and was discharged following aggressive treatment of subcutaneous exhaust and thoracic closed drainage. Due to fiberoptic bronchoscopy was refused by the guardian to determine the cause, we hypothesized tracheal intubation injury occurs, air enter the trachea or bronchial mucosa, extend up to the neck, head and face along the blood vessels, larynx and deep cervical fascia spaces, causing subcutaneous emphysema, and then gradually spread to the mediastinum, resulting in mediastinal emphysema and pneumothorax. However, the etiology and preventive measures warrant further study. Strengthen the etiological study of subcutaneous and/or mediastinal emphysema and pneumothorax due to endotracheal intubation, perioperative observation and postoperative follow-up are important measures for the effective prevention, early diagnosis, and timely treatment of subcutaneous and/or mediastinal emphysema and pneumothorax, and are also conducive to ensuring the safety of patients.

Targeted chemotherapy in retinoblastoma: A step forward from patient survival to globe survival.

Despite being the most common intraocular malignancy in childhood, there is a substantial disparity between developing and developed countries in terms of patient and globe survival in retinoblastoma (Rb). The current study intends to determine patient and globe survival before and after the introduction of the new targeted treatment modalities in a developing country. Medical records of 350 patients (516 eyes) with retinoblastoma referred to a tertiary referral center for Rb in Tehran, Iran, were reviewed. In order to compare patient and globe survival before and after the availability of the new treatment modalities, including intra-arterial and intravitreal chemotherapy, the patients were divided into group 1 (2001-2007) and group 2 (2008-2018) based on the calendar period of diagnosis. Two-hundred-twenty-three eyes of 149 patients and 293 eyes of 201 patients were categorized into groups 1 and 2, respectively. The 5-year patient survival was 97% across the current survey, and the overall survival rate was 96% in group 1 and 99% in group 2 (P = 0.08). Overall, 50% of eyes with retinoblastoma underwent enucleation, which was the primary in 63% (116/184) of the unilateral and 30% (99/322) of the bilateral cases. Primary enucleation was significantly lower in group 2 (35%) in contrast to group 1 (50%) (P < 0.001). In addition, globe survival improved significantly in the International Classification of Retinoblastoma Groups D (17% in group 1 vs. 66% in group 2, P < 0.001) and E (1% in group 1 vs. 23% in group 2 P < 0.001) during the two timelines. In enucleated eyes, despite the increased rate of prelaminar involvement in group 2 (13% vs. 2% in group 1, P = 0.003), the rate of high-risk histopathologic findings was similar between the two groups. Similar to developed countries, the application of new targeted treatment modalities, including intra-arterial and intravitreal chemotherapy, has been associated with significantly improved globe survival in Rb patients. However, it should be noted that even with the availability of these novel treatment options, the decision for on-time enucleation should not be deferred.

Prospective Determination of Orbital Perfusion Dominance before Intra-Arterial Chemotherapy for Retinoblastoma Using Time-of-Flight Magnetic Resonance Angiography

AbstractIntra-arterial chemotherapy (IAC) represents a mainstay in the treatment of retinoblastoma. In a minority of cases, the external carotid artery (ECA) serves as the dominant supply to the central retinal artery and is associated with prolonged fluoroscopy times and higher intraprocedural radiation doses. The aim of this study was to evaluate the utility of time-of-flight (TOF) magnetic resonance angiography (MRA) for prospective determination of internal (ICA) versus ECA dominance for procedural planning. Between April 2017 and December 2020 (44 months), staging MR prior to IAC for retinoblastoma included variant spatial saturation band position TOF angiography. Exams were then retrospectively reviewed for concordance of ICA versus ECA dominance between the two modalities. Eight consecutive patients were included in the study. Mean patient age at time of diagnosis was 20.3 ± 10.7 months (range: 2.7–33.2 months). Ten affected eyes were included (2 cases of bilateral disease), with stage D disease in eight eyes and stage B disease in two eyes. MRA techniques demonstrated antegrade ophthalmic artery (OA) flow in 9/10 (90%) of affected eyes. Subsequent catheter angiography confirmed ICA dominant supply in 9/9 (100%). For a single affected eye (10%), the OA was demonstrated as orthotopic by T2 flow void, nonvisualized on anterior saturation TOF sequences, and faintly visualized on posterior saturation TOF sequences. Aggregate MRA to catheter angiographic concordance was 10/10 (100%). Variant saturation TOF MRA predicts ICA versus ECA dominant supply to the central retinal artery in retinoblastoma.

The Safety and Effectiveness of Melphalan-Based Intra-Arterial Chemotherapy for Retinoblastoma: An Updated Single-Arm Systematic Review and Meta-Analysis.

Melphalan-based intra-arterial chemotherapy was considered an innovative treatment for retinoblastoma patients because high rates of globe salvage could be obtained. Now it has been widely applied for primary or secondary treatment of retinoblastoma. This meta-analysis summarizes the most up-to-date evidence regarding the safety and effectiveness of melphalan-based intra-arterial chemotherapy in the treatment of retinoblastoma. The authors searched PubMed, EMBASE, and the Web of Science electronic databases for studies investigating the safety and effectiveness of melphalan-based intra-arterial chemotherapy in the treatment of retinoblastoma. Studies reporting outcomes and complications of melphalan-based intra-arterial chemotherapy for the treatment of retinoblastoma patients would be included. A total of 33 observational studies that involved 1900 patients and 2336 eyes were included. The overall globe salvage rate was 79.6% (773/971 eyes, 0.74 [95% CI: 0.66, 0.80]) for patients treated with IAC as primary therapy in 28 studies. The overall globe salvage rate was 66.4% (923/1391 eyes, 0.68 [95% CI: 0.60, 0.76]) for patients treated with IAC as secondary therapy in 25 studies. The most common ocular complications were retinopathy (32%) and palpebral edema (29.7%). The most common systemic complications were nausea/vomiting (20.9%). The overall metastasis rate was 1.1% (21/1793 patients, 0.038 [95% CI: 0.020, 0.038]). Twenty-nine studies that involved 1783 patients reported the mortality and the overall mortality was 1.5% (26/1783 patients, 0.029 [95% CI: 0.020, 0.048]). Our meta-analysis showed that melphalan-based IAC treatment was an option for retinoblastoma patients with acceptable efficacy according to retrospective studies. Further high-quality randomized control trials are necessary to provide more accurate and reliable results.